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Flashcards in Renal Pathology (DN) Deck (49):
1

Diabetic Nephropathy is the leading cause of _____ in most Western societies in both DM I and II

ESRD
*risk related to duration of disease

2

Diabetics will increase risk of developing diabetic nephropahty drastically ____ to ____ years after Dx with diabets and ____ to ____ years after onset of proteinuria

20-25 yrs
2-3 yrs

3

Pathology of DN: Hyperfiltration
See increased GFR due to:

glucose dependent afferent arteriolar dilation and Ang II mediated cnx of efferent arteriole

4

As a result of hyperfiltration in early DM we see increase ________ pressure post glom
This cause wht to the Na+

increases colloid osmotic P
increase Na reabsorption in PT

5

Besides increasing GFR, what other effect does Ang II have

causes hypertrophic PT growth

6

How can we control the hyperfiltration aspect of DN?

Glycemic control!

7

Pathogeneis of DN: HYpertrophy
Seen when:
Assoicated with:

early onset w/ size of kids increasing several cm
see increased number of mesangial cells and capillary loops--> increases SA

8

Pathogenesis of DN: Mesangial Cells
Results in:

Mesangial expansion with nodular diabetic glomerulosclerosis = Kmmelsteil Wilson lesion
*mediated by glucose and AGEs
--> increased size and more ECM deposition

9

Pathogenesis DN: Proteinuria
What happens to the
1. GBM
2. Podocytes
3. Serum proteins

1. GBM accumulate type IV col and net reduction of (-) heparin sulfate
2. Podocyte feet increase width and apoptosis trig by AngII and TGF-B, also decreaed migration from Ang II
3. Serum pros cross BM from disrupted holes

10

Pathogeneis DN: Fibrosis
What do we see early on and what causes this

early on see tubulointerstitial fibrosis from GFs TGF-B and ANG II

11

In fibrosis seen in DN, tubular cells change phenotype to____

fibroblasts

12

What enhances the fibrosis process in DN

glucose concentration and AGEs

13

During Stage 1 and 2 we see ____ GFR and renal _____

Increased GFR (25-50%)
Renal hypertrophy

14

What stage do we see mesangial expansion and GBM thickening in?

Stage 2 of DN; clinically asymptomatic but see on biopsy

15

What stage is there devo of HTN, persistent microalbuminuria and urinary albumin excretion of 30-300/day?

Stage 3: Early nephropathy

16

See GFR decline, urninary albumin >300 mg/day
50% pts reash ESRD w/in 7-10 yrs and retinopathy in 95%

Stage 4: Overt proteinuria

17

Renal replacement therapy necessary, seen about 15 ys after onset of Type I DM pts with proteinuria (30%)

Stage 5: ESRD

18

Co-morbidities of DN

• HTN
• Neuropathy
• Vascular changes
• Increased mortality

19

Diabetic retinopathy
• in almost all patients with______diabetes and nephropathy.
• In 50% to 60% of ______diabetes with nephropathy

type 1
type 2

20

What polyneuropathy issues do we see with DN?

• Polyneuropathy.
• Sensory polyneuropathy: Diabetic foot
• Autonomic polyneuropathy
• Silent angina
• Gastroparesis
• erectile impotence
• detrusor paresis

21

Macrovascular complications _____ x more frequent in DN
• Stroke
• coronary heart disease
• peripheral vascular disease

(5X more frequent)

22

Key Txs for DN

• HTN therapy
• Glucose control
• Reduction of proteinuria
• Lipid lowering therapy
• Life style modification

23

• In DM pts with DN, HTN is
almost always present
• Uncontrolled hypertension is
associated with:

• more rapid progression of DN
• increased risk of fatal and
nonfatal CV events.

24

Recommended BP for all diabetics pts

140/90
• antihypertensive therapies
improve survival in both type 1
and type 2 diabetics with DN
Control glucose levels! decreases progression from normo-microalbuminuria

25

What are ways to reduce proteinuria and

• Renin-angiotensin-aldosterone system blockade
• Renoprotective independent of BP
• May cause up to 30% decline in GFR but renoprotective in the longterm

26

RAAS works through renal hemodynamic changes
and blocking non-hemodyanmic effects of

Ang II

27

• Most patients with DN have:
– Low HDL
– High TGs
– Smaller LDL particle
• In type 2 diabetic patients with DN, treatment with______ provides substantial CV benefit

statins
(–seen in DN with ESRD)

28

Current guidelines
– LDL _____mg/dl for diabetic patients in general and
____mg/dl for diabetic patients with CVD

<70

29

Lifestyle modifications
• Smoking cessation
– Decreases progression of _____
• weight reduction
– Possibly improves renal outcome via reduction in ____

micro to macro albuminuria
proteinuria

30

• Amyloidosis affecting the kidney
– light chains, secreted by a _______
• 20% of cases associated with multiple myeloma
– Usually _________

single clone of B cells

lambda light chains (AL)

31

What kidney manifestations do we see with Amyloidosis?

enlarged and hypertension is absent even when renal function is impaired.
Proteinuria, mainly albuminuria, occurs in the absence of microscopic hematuria.
Tubular defects from amyloid deposits

32

What tubular defects from amyloid deposits do we see?

– Renal tubular acidosis (mostly as a part of Fanconi syndrome)
– polyuria-polydipsia (resulting from urinary concentration defect)

33

What do we see on LM and IM on amyloidosis?

LM: see deposits and Congo-red stain: apple green birefringence
IM: staining for light chain

34

What extra-renal manifestations do we see with amyloidosis?

restrictive cardiomyopathy
GI issues
Splenomegaly
macroglossia
Peripheral nerve damage
skin
joint

35

Light Chain Deposition disease is excess ________ in kidney and 50% of cases co-exsist with _____

immunoglobuin light chain, usually Kappa
multiple myeloma

36

Pts with Light chain deposition develop

proteinuria
hematuria
chronic renal insufficiency

37

Looking at LM we see nodular glomerulosclerosis
IF: is + for Kappa staining
EM: see granular deposits along the GBM

Light Chain deposition

38

Alport Syndrome
• Most commonly ______ (80%) but can be autosomal recessive as well
• Mutation of the ____ gene on chromosome Xq22 which encodes the alpha-5
chain of _________

X-linked recessive

COL4A5

type IV collagen
*--> defect in the basement membrane

39

– Affected males have persistent microscopic hematuria
– episodic gross hematuria, precipitated by URI
– Present in the first two decades of life.

Alport syndrome

40

Most females with _____ have persistant or intermittent microscropic hematuria while only 7% of _____ never manifest hematuria

XLAS

obligate heterozygotes

41

•______ is absent early but develops eventually in all males
with XLAS and in both males and females with ARAS.

Proteinuria

42

• ESRD develops in all affected males with XLAS (90% by age 40)– rate determined by the underlying _____

COL4A5 mutation.

43

What are the extra-renal manifestations in Alport

Cochlear defects
Ocular defects--yellowish flecks or granulations in perimacular distrubtion
Leiomyomatosis

44

Pathology of AS
• LM:
• IF:
EM:

• LM: Early =normal. Later global and segmental glomerulosclerosis, interstitial fibrosis
• IF: Negative or non-specific IgM, C
EM: variable thickening, thinning, basket weaving, and lamellation of the GBM

45

Tx for Alport

RAAS blockade
Renal replacement eventually necessary
Transplant: 2-3% get anti-GMB disease

46

Inheritance pattern of Thin Basement Membrane Disease (Benign familial Hematuria)

autosomal dominance

47

• Continuous or intermittent microhematuria, with or without gross hematuria, and
generally no renal insufficiency

Thin basement membrane disease (benign familial hematuria)

48

What do we see on EM in Thin Basement Membrane Disease

• EM: Thin GBM (usually < 200 nm)

49

Tx for Thin Basement Membrane Disease

-reassurance, very small risk for ESRD
– BMP, urinalysis and BP monitored every 1-2 years